The mechanisms underlying the clinical syndrome known as CS are unkown. We and others have suggested that CFS onset and symptoms are frequently associated with infection and inflammation, including atopy as a specific type of inflammation. Patients often relate exacerbations of their illness following tiring physical activity and allergen exposure. Recent studies have suggested a link between exercise and release of cytokines and complement activation possibly as a consequence of muscle injury induced by the activity. This trigger of the syndrome is universal and its importance led to its inclusion in the 94 revision of the working definition. Triggering by exposure to a single allergen is often a patient complains, as is exacerbation of the symptoms during allergen season. This study will evaluate the role of these "triggers" in the exacerbation of this chornic illness state with the eventual goal of defining the abnormal responses which induced and perpetuate the development of CFS. Year I of this grant was designed to enroll 40 subjects, 20 of whom with CFS and 20 control subjects with 1/2 (10) in each group being allergic. As of November 30, 1998 40 individuals have been enrolled. Since the critical numbers will be acquired at the end of year 3, future enrollment will concentrate on achieving a 3:1 ratio of female to males in such group and age matches within 5 years. Recruitment is an ongoing process with a goal of 50 indivudals during year 2. The grant is still in the data gathering stage, no findings are available. Based on the study design of collecting data over a 3 year period, analysis of challenges are not expected to show meaningful results until the end of that time. Analsysis for trends will be performed during the second year, even though the numbers of subjects in each of the groups may be too small to expect definitive differences. The specific aims described in the original application remains in effect. On additional parameter includes obtaining a blood specimen before challenges for mononuclear cell RNA to be analyzed for cytokine mRNA expression using a microarray technique at the CDC as part of the ongoing CFS project at that institution. Subjects are asked to join this project as an add-on to our grant.